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Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro

The extremely poor prognosis of patients affected by glioblastoma (GBM, grade IV glioma) prompts the search for new and more effective therapies. In this regard, drug repurposing or repositioning can represent a safe, swift, and inexpensive way to bring novel pharmacological approaches from bench to...

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Autores principales: Matteoni, Silvia, Matarrese, Paola, Ascione, Barbara, Buccarelli, Mariachiara, Ricci-Vitiani, Lucia, Pallini, Roberto, Villani, Veronica, Pace, Andrea, Paggi, Marco G., Abbruzzese, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952964/
https://www.ncbi.nlm.nih.gov/pubmed/33718225
http://dx.doi.org/10.3389/fonc.2021.635472
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author Matteoni, Silvia
Matarrese, Paola
Ascione, Barbara
Buccarelli, Mariachiara
Ricci-Vitiani, Lucia
Pallini, Roberto
Villani, Veronica
Pace, Andrea
Paggi, Marco G.
Abbruzzese, Claudia
author_facet Matteoni, Silvia
Matarrese, Paola
Ascione, Barbara
Buccarelli, Mariachiara
Ricci-Vitiani, Lucia
Pallini, Roberto
Villani, Veronica
Pace, Andrea
Paggi, Marco G.
Abbruzzese, Claudia
author_sort Matteoni, Silvia
collection PubMed
description The extremely poor prognosis of patients affected by glioblastoma (GBM, grade IV glioma) prompts the search for new and more effective therapies. In this regard, drug repurposing or repositioning can represent a safe, swift, and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication used since six decades for the therapy of psychiatric disorders, shows in vitro several features that make it eligible for repositioning in cancer therapy. Using six GBM cell lines, three of which growing as patient-derived neurospheres and displaying stem-like properties, we found that chlorpromazine was able to inhibit viability in an apoptosis-independent way, induce hyperdiploidy, reduce cloning efficiency as well as neurosphere formation and downregulate the expression of stemness genes in all these cell lines. Notably, chlorpromazine synergized with temozolomide, the first-line therapeutic in GBM patients, in hindering GBM cell viability, and both drugs strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. These results prompted us to start a Phase II clinical trial on GBM patients (EudraCT # 2019-001988-75; ClinicalTrials.gov Identifier: NCT04224441) by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol.
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spelling pubmed-79529642021-03-13 Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro Matteoni, Silvia Matarrese, Paola Ascione, Barbara Buccarelli, Mariachiara Ricci-Vitiani, Lucia Pallini, Roberto Villani, Veronica Pace, Andrea Paggi, Marco G. Abbruzzese, Claudia Front Oncol Oncology The extremely poor prognosis of patients affected by glioblastoma (GBM, grade IV glioma) prompts the search for new and more effective therapies. In this regard, drug repurposing or repositioning can represent a safe, swift, and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication used since six decades for the therapy of psychiatric disorders, shows in vitro several features that make it eligible for repositioning in cancer therapy. Using six GBM cell lines, three of which growing as patient-derived neurospheres and displaying stem-like properties, we found that chlorpromazine was able to inhibit viability in an apoptosis-independent way, induce hyperdiploidy, reduce cloning efficiency as well as neurosphere formation and downregulate the expression of stemness genes in all these cell lines. Notably, chlorpromazine synergized with temozolomide, the first-line therapeutic in GBM patients, in hindering GBM cell viability, and both drugs strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. These results prompted us to start a Phase II clinical trial on GBM patients (EudraCT # 2019-001988-75; ClinicalTrials.gov Identifier: NCT04224441) by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. Frontiers Media S.A. 2021-02-26 /pmc/articles/PMC7952964/ /pubmed/33718225 http://dx.doi.org/10.3389/fonc.2021.635472 Text en Copyright © 2021 Matteoni, Matarrese, Ascione, Buccarelli, Ricci-Vitiani, Pallini, Villani, Pace, Paggi and Abbruzzese http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Matteoni, Silvia
Matarrese, Paola
Ascione, Barbara
Buccarelli, Mariachiara
Ricci-Vitiani, Lucia
Pallini, Roberto
Villani, Veronica
Pace, Andrea
Paggi, Marco G.
Abbruzzese, Claudia
Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
title Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
title_full Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
title_fullStr Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
title_full_unstemmed Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
title_short Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
title_sort anticancer properties of the antipsychotic drug chlorpromazine and its synergism with temozolomide in restraining human glioblastoma proliferation in vitro
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952964/
https://www.ncbi.nlm.nih.gov/pubmed/33718225
http://dx.doi.org/10.3389/fonc.2021.635472
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